Dr Yee on Neoadjuvant Datopotamab Deruxtecan in High-Risk, Early-Stage Breast Cancer

Douglas Yee, MD, director and the John H. Kersey Chair in Cancer Research, Masonic Cancer Center, University of Minnesota, discusses the results from a cohort of the phase 2 I-SPY2.2 trial (NCT01042379) that evaluated neoadjuvant datopotamab deruxtecan (Dato-DXd) in patients with high-risk, early-stage breast cancer.

Results presented by Jane L. Meisel, MD, of Winship Cancer Institute of Emory University during the2024 ASCO Annual Meeting showed that the trial did not reach its prespecified pathologic complete response (pCR) threshold of 85% following 4 cycles of Dato-DXd. Overall, 32% of evaluable patients (n = 103) proceeded to surgery following treatment with Dato-DXd without requiring chemotherapy.

Although the study did not meet its primary end point, Yee explains strong efficacy signals were observed in patients in different subgroups within the overall population. A pCR rate of 31% was observed in patients with HER2-negative, immune-positive breast cancer (n = 46). Similarly, a pCR rate of 29% was recording in the HER2-negative, immune-negative, DNA repair deficiency–positive subgroup (n = 10). In patients with hormone receptor (HR)–negative, HER2-positive disease (n = 50), the pCR rate was 35%; conversely, those with HR-positive, HER2-negativie disease (n = 53) experienced a pCR rate of 6%.

Among all patients, Dato-DXd was well tolerated, Yee continues. No new safety signals were reported for the antibody-drug conjugate compared with prior data for Dato-DXd from the phase 3 TROPION-Breast01 trial (NCT05104866), and adverse effects did not lead to treatment discontinuation in any patients.

Despite not reaching the anticipated threshold, the pCRs observed still indicates a potential benefit for certain patient groups, Yee explains. Ongoing efforts will focus on better defining patient populations who would derive the most benefit from Dato-DXd in the neoadjuvant setting, he says. ADCs remain a promising therapeutic avenue for patients with breast cancer, and future research will help identify areas where these agents could have an earlier impact for patients, Yee concludes.